The Inflammatory CXC Chemokines, GROαhigh, IP-10low, and MIGlow, in Tumor Microenvironment Can Be Used as New Indicators for Non-small Cell Lung Cancer Progression

Immunol Invest. 2017 May;46(4):361-374. doi: 10.1080/08820139.2017.1280052. Epub 2017 Apr 4.

Abstract

Aims: To investigate the clinical significance of tumor tissue-infiltrating chemokines expression in non-small cell lung cancer (NSCLC) microenvironment.

Materials and methods: Fresh tissue samples were acquired from 50 patients with NSCLC after operation. Then, we quantified the total protein with the BCA Protein Assay Kit and tested 13 chemotactic factors in paired samples including tumor tissues, tumor adjacent tissues, and normal tissues with the CBA Kit.

Results: We found that the chemokine CC subfamily of MCP-1, MIP-1α, MIP-1β, and MIP-3α and the chemokine CXC subfamily of IL-8, GROα, IP-10, and MIG expressions in tumor tissues were significantly higher than those in tumor-adjacent tissues and normal tissues. However, regulated upon activation normal T cell expressed and secreted (RANTES), human thymus activation regulated chemokine (TARC), chemokine (C-C motif) ligand 11 (CCL11), interferon-inducible T cell alpha chemoattractant (I-TAC), and ENA-78 expressions did not show significant difference. Analyzing the influence of chemokine expression level in tumor tissues on disease progression, we found the median progression-free survival (mPFS) of patients with GROαhigh was significantly lower than those with GROαlow; mPFS of patients with IP-10low was significantly lower than those with IP-10high; and mPFS of patients with MIGlow was significantly lower than those with MIGhigh. However, MCP-1, MIP-1α, MIP-1β, MIP-3α, and IL-8 had no significant value to elevate the mPFS of patients with NSCLC.

Conclusion: In summary, tumor tissue-infiltrating CXC chemokines, GROαhigh, IP-10low, and MIGlow in the tumor microenvironment can be used as potential indicators for the progression of NSCLC.

Keywords: Chemokines; NSCLC; PFS; progression; tumor microenvironment.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism*
  • Carcinogenesis
  • Carcinoma, Non-Small-Cell Lung / diagnosis*
  • Chemokine CXCL1 / metabolism*
  • Chemokine CXCL10 / metabolism*
  • Chemokine CXCL9 / metabolism*
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Humans
  • Lung / metabolism*
  • Lung Neoplasms / diagnosis*
  • Male
  • Middle Aged
  • Tumor Microenvironment

Substances

  • Biomarkers, Tumor
  • CXCL10 protein, human
  • CXCL9 protein, human
  • Chemokine CXCL1
  • Chemokine CXCL10
  • Chemokine CXCL9